The Clinical Mass Spectrometry Core collaborates with investigators from across the NIDDK Clinical Research Program, NIDDK basic research program and collaborating institutes to conduct stable isotope tracer studies (human and mammalian sources). Clinical studies using stable isotopes involve administering a subject with substances labeled with rare, non-radioactive, stable isotopes, collecting samples, and monitoring production or decay of the isotopic ratio of the labeled product. Stable isotopes are advantageous for clinical studies as they are essentially chemically and physically indistinguishable from the predominant natural isotope of the same element, however, they are readily distinguished and quantitated by mass spectrometers. The most commonly used stable isotopes are hydrogen(2H), oxygen(18O) and carbon(13C) The doubly labeled water (DLW) method was developed to measure total energy expenditure. A person or animal is administered a dose of water enriched in deuterium, and 18-oxygen. Labeled hydrogen can only be lost through water, whereas oxygen can be lost as water or carbon dioxide. Calculating the rate of carbon dioxide production then yields a measure of total energy expenditure. Metabolic studies with stable isotopes cover a vast range. Currently we measure labeled glucose, glycerol, and free fatty acids. The lab will advise, develop and validate novel research assays in collaboration with on-going clinical research projects and actively seeks new areas for collaboration with staff from across the NIH community. The most common projects nowadays involve mass spectrometry quantitation, by GC-MS but especially by LC-MS, of many drugs, metabolites, or small molecule compounds. Beside quantitation, we have identified unknown metabolite or even contaminants, which provided new avenues for investigation.